An update on the pharmacological management and prevention of cerebral edema: current therapeutic strategies

ABSTRACT

Introduction: Cerebral edema is a common complication of multiple neurological diseases and is a strong predictor of outcome, especially in traumatic brain injury and large hemispheric infarction.

Areas Covered: Traditional and current treatments of cerebral edema include treatment with osmotherapy or decompressive craniectomy at the time of clinical deterioration. The authors discuss preclinical and clinical models of a variety of neurological disease states that have identified receptors, ion transporters, and channels involved in the development of cerebral edema as well as modulation of these receptors with promising agents.

Expert opinion: Further study is needed on the safety and efficacy of the agents discussed. IV glibenclamide has shown promise in preclinical and clinical trials of cerebral edema in large hemispheric infarct and traumatic brain injury. Consideration of underlying pathophysiology and pharmacodynamics is vital, as the synergistic use of agents has the potential to drastically mitigate cerebral edema and secondary brain injury thusly transforming our treatment paradigms.

KEYWORDS:

• Cerebral edema
• glibenclamide
• large hemispheric infarction
• traumatic brain injury

Article highlights

• Cerebral edema contributes to the high morbidity and mortality seen in large hemispheric infarction (LHI), traumatic brain injury (TBI), and other neurological diseases.

• To date, osmotherapy and surgical decompression remain the mainstays of therapy.

• Multiple receptors, ion transporters, and channels have been implicated in formation of cerebral edema, including NKCC1, aquaporins, vasopressin receptors, matrix metalloproteinases, sphingosine-1-phosphate, and SUR1-TRPM4.

• Emerging preclinical and clinical data have shown promise in modulating these receptors as potential treatment targets for novel antiedema drugs.

This box summarizes key points contained in the article.

Declaration of interest

N Badjatia is supported by a grant from the National Institute of Neurological Disorders and Stroke (NINDS) (R01NS105503). JM Simard is supported by grants from the Department of Veterans Affairs (I01RX003060, I01BX004652), the Department of Defense (SCI170199), the National Heart, Lung and Blood Institute (R01HL082517) and the NINDS (R01NS102589; R01NS105633). JM Simard holds a US patent (7,285,574), ‘A novel non-selective cation channel in neural cells and methods for treating brain swelling.’ He is also a member of the Board of Directors and holds shares in Remedy Pharmaceuticals and is a paid consultant for Biogen Idec. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.